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Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
JACC. Advances Dec 2023Statins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged.
BACKGROUND
Statins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged.
OBJECTIVES
The objective of this study was to compare an active vs a passive strategy (ie, usual care) to statin prescription for primary prevention of atherosclerotic cardiovascular disease (ASCVD).
METHODS
A total of 3,770 patients ≥50 years of age without a history of ASCVD or statin use were invited to enroll in CorCal, with 601 consenting to participate. These patients were randomized 1:1 to statin initiation guided by the pooled cohort equation or by coronary artery calcium scoring (CACS). Outcomes (2.8-year follow-up) compared patients managed actively vs passively (randomly invited but declined or did not respond).
RESULTS
Patient demographics were well matched. Statin recommendation was common among enrolled patients (41.7%). During follow-up, 25.3% of active patients were taking a statin vs 9.8% managed passively ( < 0.0001). Active patients had more lipid panels (median 2.0 vs 1.0), lower low-density lipoprotein cholesterol (109 vs 117 mg/dL) (both < 0.0001), and a low rate of major adverse cardiovascular events during follow-up (0.6% vs 1.0%, = 0.47). Statistical comparisons included -tests, chi-squared tests, nonparametric tests, and time-to-event tests as appropriate.
CONCLUSIONS
An active approach to statin selection for primary ASCVD prevention identified a large treatment opportunity and led to over twice as many patients on statins compared to passive (usual care) management. A large CorCal Outcomes Trial is underway to more definitively assess the impact on outcomes of active management of statins for primary prevention.
PubMed: 38938499
DOI: 10.1016/j.jacadv.2023.100676 -
Primary Atherosclerotic Cardiovascular Disease Prevention: Optimally Active, Agile, and Accountable.JACC. Advances Dec 2023
PubMed: 38938487
DOI: 10.1016/j.jacadv.2023.100677 -
JACC. Advances Oct 2023
PubMed: 38938370
DOI: 10.1016/j.jacadv.2023.100615 -
JACC. Advances Oct 2023Mobile health (mHealth) interventions are increasingly being used for cardiovascular research and physical activity promotion.
BACKGROUND
Mobile health (mHealth) interventions are increasingly being used for cardiovascular research and physical activity promotion.
OBJECTIVES
As a result, the authors aimed to evaluate which features facilitate and impede routine engagement with mobile fitness applications.
METHODS
We distributed a pan-Canadian online questionnaire via the behavioral research platform Prolific.co to evaluate what features are associated with the use and routine engagement (ie, daily or weekly use) of mHealth fitness applications and attitudes about data sharing. Binary logistic regression was used to quantify the association between these endpoints and exploratory factors such as the perceived utility of various mHealth application features.
RESULTS
The survey received 694 responses. Most people were women (62%), the median age was 28 years (range: 18-78 years), and most people reported current use of an mHealth fitness application (48%). The perceived importance of personal health (OR: 2.40; 95% CI: 1.34-4.50) was the factor most associated with the current use of an mHealth fitness application. The feature most associated with routine engagement was the ability to track progress toward a goal (OR: 5.10; 95% CI: 2.73-9.61) while the most significant barrier was the absence of goal customization features (OR: 0.44; 95% CI: 0.25-0.81). The acceptance of sharing health data for research was high (56%), and privacy concerns did not significantly affect routine engagement (OR: 0.81; 95% CI: 0.40-1.77). Results were consistent across race and gender.
CONCLUSIONS
mHealth interventions have the potential to be scaled across populations. Optimizing applications to improve self-monitoring and personalization could increase routine engagement and, thus, user retention and intervention effectiveness.
PubMed: 38938369
DOI: 10.1016/j.jacadv.2023.100613 -
JACC. Advances Oct 2023Thromboprophylaxis for medically ill patients during hospitalization and postdischarge remains underutilized. Clinical decision support (CDS) may address this need if...
BACKGROUND
Thromboprophylaxis for medically ill patients during hospitalization and postdischarge remains underutilized. Clinical decision support (CDS) may address this need if embedded within workflow, interchangeable among electronic health records (EHRs), and anchored on a validated model.
OBJECTIVES
The purpose of this study was to assess the clinical impact of a universal EHR-integrated CDS tool based on the International Medical Prevention Registry on Venous Thromboembolism plus D-Dimer venous thromboembolism model.
METHODS
This was a cluster randomized trial of 4 tertiary academic hospitals from December 21, 2020 to January 21, 2022. Inpatients over age 60 with key medical illnesses were eligible. We embedded CDS at admission and discharge. Hospitals were randomized to intervention (CDS; n = 2) vs usual care (n = 2) groups. The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included venous, arterial, and total thromboembolism, major bleeding, and all-cause mortality through 30 days postdischarge.
RESULTS
After exclusions, 10,699 of 19,823 patients were analyzed. Intervention group tool adoption was 77.8%. Appropriate thromboprophylaxis was increased at intervention hospitals, both inpatient (80.1% vs 72.5%, OR: 1.52, 95% CI: 1.39-1.67) and at discharge (13.6% vs 7.5%, OR: 1.93, 95% CI: 1.60-2.33). There were fewer venous (2.7% vs 3.3%, OR: 0.80, 95% CI: 0.64-1.00), arterial (0.25% vs 0.70%, OR: 0.35, 95% CI: 0.19-0.67), and total thromboembolisms (2.9% vs 4.0%, OR: 0.71, 95% CI: 0.58-0.88) at intervention hospitals. Major bleeding was rare and did not differ between groups. Mortality was higher at intervention hospitals (9.1% vs 7.0%, OR: 1.32, 95% CI: 1.15-1.53).
CONCLUSIONS
EHR-embedded CDS increased appropriate thromboprophylaxis and reduced thromboembolism without increasing major bleeding in medically ill inpatients. Mortality was higher at intervention hospitals.
PubMed: 38938337
DOI: 10.1016/j.jacadv.2023.100597 -
JACC. Advances Jun 2023The use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk,...
BACKGROUND
The use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients.
OBJECTIVES
The purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF).
METHODS
Intermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes.
RESULTS
A total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE ( < 0.0001).
CONCLUSIONS
These results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.
PubMed: 38938227
DOI: 10.1016/j.jacadv.2023.100385 -
Journal of Preventive Medicine and... Jun 2024A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression,...
OBJECTIVES
A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression, anxiety, and obsessive-compulsive disorder, are prevalent. Identifying causes and associated risk factors is imperative for early intervention and the prevention of mental health issues.
METHODS
This study utilized data from the 2018 Basic Health Research, which was conducted nationwide in Indonesia, using a cross-sectional approach. We focused on women aged 13-49 years who were currently or previously married, and had experienced pregnancy, including 8,889 pregnant women and 77,012 women who had delivered between January 1, 2013, and August 31, 2018. The Self-Reporting Questionnaire-20 was employed to assess CMDs. Multivariate logistic regression was performed.
RESULTS
The prevalence of CMDs in pregnant women was 12.6%, while postpartum mothers exhibited a prevalence of 10.1%. Poor health status displayed the strongest impact on CMDs during both pregnancy (Adjusted Odds Ratio [AOR]: 12.23, 95% Confidence Interval [CI]: 9.06-16.60) and the postpartum period (AOR: 16.72, 95% CI: 14.85-18.82). Additional significant factors for both group include young maternal age, lack of education, unemployment, hystory of hypertension, and smoking status. Among pregnant women, CMDs was also associated with first-trimester pregnancy, previous pregnancy complications, and small upper arm circumference. For postpartum mothers, significant factors include history of abortion, unwanted pregnancy, pregnancy complications, lack of antenatal care, spontaneous delivery, postpartum complications and contraceptive use.
CONCLUSIONS
CMDs can impact in pregnant and postpartum women. Early diagnosis and management must be seamlessly integrated into primary healthcare practices.
PubMed: 38938048
DOI: 10.3961/jpmph.24.082 -
Journal of Preventive Medicine and... Jun 2024Comorbidities increase susceptibility to severe coronavirus disease 2019 (COVID-19) infections, but limited information has been published regarding HIV and COVID-19...
OBJECTIVES
Comorbidities increase susceptibility to severe coronavirus disease 2019 (COVID-19) infections, but limited information has been published regarding HIV and COVID-19 co-infections. This study explored the relationships among socioeconomic characteristics, sexual behaviors, and COVID-19 infection rates among Korean men who have sex with men (MSMs) who are also living with HIV.
METHODS
Data were collected through a web survey aimed at members of the largest gay portal site in Korea, supported by the National Research Foundation of Korea (n=1,005). The primary independent variables included COVID-19-related vaccinations and sexual behaviors. The dependent variable was the incidence of COVID-19 infection among respondents during the pandemic. For statistical analysis, hierarchical multiple logistic regression was performed, controlling for potential confounding variables.
RESULTS
Model I indicated that older MSM were less likely to contract COVID-19 (adjusted odds ratio [aOR], 0.975; 95% CI, 0.962-0.989). Model II demonstrated that HIV-positive MSM were nearly twice as likely to be infected with COVID-19 compared to their HIV-negative counterparts (aOR, 1.974; 95% CI, 1.144-3.408). Furthermore, even after accounting for COVID-19 vaccination status in model III, HIV-positive MSM continued to show a higher risk of infection (aOR, 1.934; 95% CI, 1.118-3.346).
CONCLUSIONS
The findings of this study indicate that HIV-positive MSM are at an increased risk of contracting COVID-19, even when their vaccination status is considered. Therefore, it is essential to prioritize the prevention of COVID-19 infections in HIV-positive individuals by administering appropriate antiretroviral therapy and ensuring adherence to public health guidelines.
PubMed: 38938044
DOI: 10.3961/jpmph.24.196 -
Immunity, Inflammation and Disease Jun 2024The COVID-19 pandemic has taken many forms and continues to evolve, now around the Omicron wave, raising concerns over the globe. With COVID-19 being declared no longer... (Review)
Review
New variants of COVID-19 (XBB.1.5 and XBB.1.16, the "Arcturus"): A review of highly questioned concerns, a brief comparison between different peaks in the COVID-19 pandemic, with a focused systematic review on expert recommendations for prevention, vaccination, and treatment measures in the general...
INTRODUCTION
The COVID-19 pandemic has taken many forms and continues to evolve, now around the Omicron wave, raising concerns over the globe. With COVID-19 being declared no longer a "public health emergency of international concern (PHEIC)," the COVID pandemic is still far from over, as new Omicron subvariants of interest and concern have risen since January of 2023. Mainly with the XBB.1.5 and XBB.1.16 subvariants, the pandemic is still very much "alive" and "breathing."
METHODS
This review consists of five highly concerning questions about the current state of the COVID Omicron peak. We searched four main online databases to answer the first four questions. For the last one, we performed a systematic review of the literature, with keywords "Omicron," "Guidelines," and "Recommendations."
RESULTS
A total of 31 articles were included. The main symptoms of the current Omicron wave include a characteristically high fever, coughing, conjunctivitis (with itching eyes), sore throat, runny nose, congestion, fatigue, body ache, and headache. The median incubation period of the symptoms is shorter than the previous peaks. Vaccination against COVID can still be considered effective for the new subvariants.
CONCLUSION
Guidelines recommend continuation of personal protective measures, third and fourth dose boosters, along with administration of bivalent messenger RNA vaccine boosters. The consensus antiviral treatment is combination therapy using Nirmatrelvir and Ritonavir, and the consensus for pre-exposure prophylaxis is Tixagevimab and Cilgavimab combination. We hope the present paper raises awareness for the continuing presence of COVID and ways to lower the risks, especially for at-risk groups.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Vaccination; Pandemics; Antiviral Agents; COVID-19 Drug Treatment
PubMed: 38938013
DOI: 10.1002/iid3.1323